In this study, we aimed to investigate the role of spinal CC chemokine ligand 5 (CCL5) in the development of bone cancer pain (BCP). A BCP model was established by inoculation of Walker 256 cells into the intramedullary space of rat tibia. The levels of spinal CCL5 mRNA and protein expression significantly and time dependently increased in BCP rats compared with sham rats. On day 15 after inoculation, intrathecal administration of anti-CCL5 neutralizing antibody (4 μg) significantly attenuated the established mechanical hyperalgesia in the Walker 256 cells-injected rats, and the effect was abolished by intrathecal pre-treatment with recombinant rat CCL5 (0.2 μg). These results suggest that the spinal CCL5 may be involved in the development of BCP. The findings of this study may provide an evidence for developing novel analgesic agents to treat BCP.
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http://dx.doi.org/10.1111/bcpt.12099 | DOI Listing |
Neuron
January 2025
Molecular Neuroregeneration, Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK. Electronic address:
Spinal cord injury (SCI) increasingly affects aged individuals, where functional impairment and mortality are highest. However, the aging-dependent mechanisms underpinning tissue damage remain elusive. Here, we find that natural killer-like T (NKLT) cells seed the intact aged human and murine spinal cord and multiply further after injury.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Anatomy, Cellular and Molecular Research Group, Faculty of Medicine, Masaryk University, Kamenice 3, CZ-625 00 Brno, Czech Republic.
CXCL12 and CXCR4 proteins and mRNAs were monitored in the dorsal root ganglia (DRGs) of lumbar (L4-L5) and cervical (C7-C8) spinal segments of naïve rats, rats subjected to sham operation, and those undergoing unilateral complete sciatic nerve transection (CSNT) on post-operation day 7 (POD7). Immunohistochemical, Western blot, and RT-PCR analyses revealed bilaterally increased levels of CXCR4 protein and mRNA in both lumbar and cervical DRG neurons after CSNT. Similarly, CXCL12 protein levels increased, and CXCL12 mRNA was upregulated primarily in lumbar DRGs ipsilateral to the nerve lesion.
View Article and Find Full Text PDFImmunol Res
January 2025
Milwaukee Institute for Drug Discovery, Department of Chemistry & Biochemistry, University of Wisconsin-Milwaukee, 2000 E Kenwood Blvd, Milwaukee, WI, 53211, USA.
Chronic muscle fatigue is a condition characterized by debilitating muscle weakness and pain. Based on our recent finding to study the potential effect of mTOR on ATG13 inactivation in chronic muscle fatigue, we report that biweekly oral administration with MHY1485, a potent inducer of mTOR, develops chronic illness in mice resulting in severe muscle weakness. As a mechanism, we observed that MHY1485 feeding impaired ATG13-dependent autophagy, caused the infiltration of inflammatory M1 macrophages (Mφ), upregulated IL6 and RANTES by STAT3 activation, and augmented demyelination in muscle-serving nerve fibers.
View Article and Find Full Text PDFJ Nanobiotechnology
January 2025
Department of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, Zhejiang, China.
Recovery from spinal cord injury (SCI) is often impeded by neuroinflammation, scar formation, and limited axonal regeneration. To tackle these issues, we developed an innovative biomimetic drug delivery system using liquid nitrogen-treated M2 macrophages (LNT M2) which internalized paclitaxel (PTX) nanoparticles beforehand. These were incorporated into a gelatin methacryloyl (GelMA) scaffold, creating a multifunctional, injectable treatment for single-dose administration.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
January 2025
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China. Electronic address:
Adhesive arachnoiditis (AA) is a rare form of chronic degenerative pathology associated with persistent inflammation in the arachnoid matter of the spinal cord. Despite the existing knowledge, the detailed pathological mechanisms underlying AA are not fully understood. This study aimed to elucidate through comprehensive single nuclei RNA sequencing (snRNA-seq) to delineate the transcriptomic landscape of AA.
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